This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by VanHulle, K.
Right arrow Articles by Malkova, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by VanHulle, K.
Right arrow Articles by Malkova, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2007, p. 2601-2614, Vol. 27, No. 7
0270-7306/07/$08.00+0     doi:10.1128/MCB.01740-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements{triangledown} ,{dagger}

Kelly VanHulle,1 Francene J. Lemoine,2 Vidhya Narayanan,3 Brandon Downing,1 Krista Hull,1 Christy McCullough,1 Melissa Bellinger,1 Kirill Lobachev,3 Thomas D. Petes,2 and Anna Malkova1*

Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202,1 Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710,2 School of Biology, Georgia Institute of Technology, Atlanta, Georgia 303323

Received 14 September 2006/ Returned for modification 14 October 2006/ Accepted 12 January 2007

Inverted DNA repeats are known to cause genomic instabilities. Here we demonstrate that double-strand DNA breaks (DSBs) introduced a large distance from inverted repeats in the yeast (Saccharomyces cerevisiae) chromosome lead to a burst of genomic instability. Inverted repeats located as far as 21 kb from each other caused chromosome rearrangements in response to a single DSB. We demonstrate that the DSB initiates a pairing interaction between inverted repeats, resulting in the formation of large dicentric inverted dimers. Furthermore, we observed that propagation of cells containing inverted dimers led to gross chromosomal rearrangements, including translocations, truncations, and amplifications. Finally, our data suggest that break-induced replication is responsible for the formation of translocations resulting from anaphase breakage of inverted dimers. We propose a model explaining the formation of inverted dicentric dimers by intermolecular single-strand annealing (SSA) between inverted DNA repeats. According to this model, anaphase breakage of inverted dicentric dimers leads to gross chromosomal rearrangements (GCR). This "SSA-GCR" pathway is likely to be important in the repair of isochromatid breaks resulting from collapsed replication forks, certain types of radiation, or telomere aberrations that mimic isochromatid breaks.

* Corresponding author. Mailing address: Biology Department, IUPUI, 723 West Michigan Street, Indianapolis, IN 46202-5132. Phone: (317) 278-5717. Fax: (317) 274-2946. E-mail: amalkova{at}iupui.edu.

{triangledown} Published ahead of print on 22 January 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, April 2007, p. 2601-2614, Vol. 27, No. 7
0270-7306/07/$08.00+0     doi:10.1128/MCB.01740-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Smith, C. E., Lam, A. F., Symington, L. S. (2009). Aberrant Double-Strand Break Repair Resulting in Half Crossovers in Mutants Defective for Rad51 or the DNA Polymerase {delta} Complex. Mol. Cell. Biol. 29: 1432-1441 [Abstract] [Full Text]  
  • Jain, S., Sugawara, N., Lydeard, J., Vaze, M., Tanguy Le Gac, N., Haber, J. E. (2009). A recombination execution checkpoint regulates the choice of homologous recombination pathway during DNA double-strand break repair. Genes Dev. 23: 291-303 [Abstract] [Full Text]  
  • Lemoine, F. J., Degtyareva, N. P., Kokoska, R. J., Petes, T. D. (2008). Reduced Levels of DNA Polymerase {delta} Induce Chromosome Fragile Site Instability in Yeast. Mol. Cell. Biol. 28: 5359-5368 [Abstract] [Full Text]  
  • Argueso, J. L., Westmoreland, J., Mieczkowski, P. A., Gawel, M., Petes, T. D., Resnick, M. A. (2008). From the Cover: Double-strand breaks associated with repetitive DNA can reshape the genome. Proc. Natl. Acad. Sci. USA 105: 11845-11850 [Abstract] [Full Text]  
  • Deem, A., Barker, K., VanHulle, K., Downing, B., Vayl, A., Malkova, A. (2008). Defective Break-Induced Replication Leads to Half-Crossovers in Saccharomyces cerevisiae. Genetics 179: 1845-1860 [Abstract] [Full Text]  
  • Vernon, M., Lobachev, K., Petes, T. D. (2008). High Rates of "Unselected" Aneuploidy and Chromosome Rearrangements in tel1 mec1 Haploid Yeast Strains. Genetics 179: 237-247 [Abstract] [Full Text]  
  • Cortes-Ledesma, F., Tous, C., Aguilera, A. (2007). Different genetic requirements for repair of replication-born double-strand breaks by sister-chromatid recombination and break-induced replication. Nucleic Acids Res 35: 6560-6570 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»